The goals of this project are: (1) to establish and define a cell culture transformation system for identification of carcinogenic agents and humans at high risk for cancer; (2) to develop human cell transformation systems, with particular emphasis on epithelial cells, in order to study host factors regulating cell transformation and the mechanisms of carcinogenesis by chemicals, viruses, hormones and x-irradiation; (3) to isolate and characterize oncogenes from human or primate tumors; and (4) to develop and test measures to prevent and/or control cell transformation and the neoplastic event for eventual clinical application. Major findings were: (1) Malignant transformation of human primary epithelial cells in culture by the combined action of a DNA hybrid virus (adenovirus 12-SV40 [Ad12-SV40]) and a retrovirus (Kirsten murine sarcoma virus [Ki-MSV]), supporting a multistep process for neoplastic conversion. (2) The addition of thyroid hormone optimized transformation by Ki-MSV and was found to exert its effects during the early phase of Ki-MSV-induced transformation. (3) Hydrocortisone was found to enhance expression of Epstein Barr virus (EBV) genomes in human cells and led to increased levels of EBV antigen expression and virus production..